The cancer risk and associated public concern with exposures to alpha-emitting radionuclides, such as americium, plutonium, thorium, radium and others is well recognized. Current protection models are based largely on statistical assumptions with little biological data. We have developed biokinetic models that fit the experimental data, and will now test these models in the human and determine the localization, distribution and dosimetry of plutonium in archived skeletal tissues now available from Russian nuclear workers. Both experimental and human data will be used to extend our current biokinetic, dosimetric and risk models to the human. The aims are: 1) To determine in canine materials the deposition and local radiation doses to tissues and cells as a function of time after exposure to plutonium. Neutron induced (NIAR) and conventional autoradiographic methods will be used. A biokinetic model will be constructed. 2) To develop an "age quality factor" for exposures to plutonium. Our studies demonstrate important age-dependent biological determinants of nuclide uptake, retention and subsequent risk. These include bone growth, bone remodeling and hematopoiesis and vascularization. 3) The localization, distribution and radiation doses to tissues and cells from 239-Pu will be determined in human tissues using NIAR. Materials will be obtained from archives of both U.S. and more highly exposed Russian workers. 4) To correlate worker exposure and occupational and clinical history with the localization and distribution of 239-Pu in archived human skeletal samples (U.S. and Russian). To determine the influence of late chronic diseases on the redistribution of Pu among organ systems. These data may substantially alter current dosimetry and risk models. 5) Determine the tissue localization of 241-Am vs. 239-Pu. This will provide insights into the cells at risk for transformation and also more biokinetic information on 241-Am, an important byproduct of nuclear technologies. 6) Data from aims 3 and 4 with human data will be used to test human models of alpha exposure from plutonium. Gaps in the model will be filled with data from experimental studies from Aims 1,2 and 5. 7) To develop a general risk model for alpha-induced neoplasms. For this, data in human and experimental studies on radium will be used as a basis for extrapolation to other alpha-emitting nuclides.